The ultimate goal of this program is to obtain data which can be used to determine the present or potential role of inhibitors of environmental chemical carcinogens in preventing neoplasia. Pursuant to this goal are several major objectives. The first is to identify inhibitors of chemical carcinogenesis. The second is to determine the mechanisms of inhibition by compounds having an inhbitory effect. The third is to determine chemical characteristics which control the ability of compounds to inhibit chemical carcinogenesis with the further goal of producing inhibitors with maximum effectiveness. The fourth is to determine conditions under which inhibition occurs. In the present renewal, studies are proposed to identify the metabolites of three phenols, i.e. 2-tert-butyl-4-hydroxyanisole, 3-tert-butyl-4-hydroxyanisole and 4-hydroxyanisole, that inhibit carcinogen-induced neoplasia. The effects of the metabolites on carcinogen-metabolizing systems, and the capacities of the metabolities to prevent neoplasia, will be ascertained. A knowledge of the active species of the three phenols which are responsible for their inhibitory effects has potential value for obtaining maximum prevention of carcinogen-induced neoplasia. A second set of investigations are proposed. This work is aimed at inhibiting the effects of reactive species of carcinogens within the gastrointestinal tract. For this purpose, we propose to use high molecular weight electrophile scavengers which will not be absorbed from the alimentary tract. The syntheses of compounds of this nature are outlined. Following synthesis, prerequisite properties and carcinogen-inhibitory capacities will be investigated.